Allotypes refer to the presence of different antigenic variants of immunoglobulin (Ig) in a given species. We have observed transient production of allotypes in mice that normally do not produce such markers or that were bred to exclude them. The molecular basis of these unexpected allotypes is not understood; they may be coded by Ig germline genes that are normally silent or by somatic variants of germline genes. Either alternative has interesting implications for how the immune system may be self-regulated. Therefore, the major aim of the proposed investigations is to ascertain which alternative is correct. In addition, a number of experiments will deal with specific means and models (nude allotype-congenic mice) for revealing unexpected allotypes. It may be that unexpected allotypes are normally kept hidden by regulatory T cells. Consistent with this idea is our recent demonstration of T cells that prevent allotype production as a result of recognizing lymphocyte antigens controlled by allotype-linked genes. Such antigens may distinguish different populations of lymphocytes and serve as recognition structures for regulatory T cells; therefore, we will attempt to characterize these antigens.